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Title: Whole-Genome Approach Discovers Novel Genetic and Nongenetic Variance Components Modulated by Lifestyle for Cardiovascular Health
Contributor(s): Zhou, Xuan (author); Van Der Werf, Julius  (author)orcid ; Carson-Chahhoud, Kristin (author); Ni, Guiyan  (author); McGrath, John (author); Hypponen, Elina (author); Lee, S Hong  (author)
Publication Date: 2020-04-21
Early Online Version: 2020-04-20
Open Access: Yes
DOI: 10.1161/JAHA.119.015661
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Both genetic and nongenetic factors can predispose individuals to cardiovascular risk. Finding ways to alter these predispositions is important for cardiovascular disease prevention.

Methods and Results

We used a novel whole genome approach to estimate the genetic and nongenetic effects on-and hence their predispositions to-cardiovascular risk and determined whether they vary with respect to lifestyle factors such as physical activity, smoking, alcohol consumption, and dietary intake. We performed analyses on the ARIC (Atherosclerosis Risk in Communities) Study (N=6896-7180) and validated findings using the UKBB (UK Biobank, N=14 076-34 538). Lifestyle modulation was evident for many cardiovascular traits such as body mass index and resting heart rate. For example, alcohol consumption modulated both genetic and nongenetic effects on body mass index, whereas smoking modulated nongenetic effects on heart rate, pulse pressure, and white blood cell count. We also stratified individuals according to estimated genetic and nongenetic effects that are modulated by lifestyle factors and showed distinct phenotype-lifestyle relationships across the stratified groups. Finally, we showed that neglecting lifestyle modulations of cardiovascular traits would on average reduce single nucleotide polymorphism heritability estimates of these traits by a small yet significant amount, primarily owing to the overestimation of residual variance.


Lifestyle changes are relevant to cardiovascular disease prevention. Individual differences in the genetic and nongenetic effects that are modulated by lifestyle factors, as shown by the stratified group analyses, implies a need for personalized lifestyle interventions. In addition, single nucleotide polymorphism–based heritability of cardiovascular traits without accounting for lifestyle modulations could be underestimated.
Publication Type: Journal Article
Grant Details: NHMRC/1080157
Source of Publication: Journal of the American Heart Association, 9(8), p. 1-16
Publisher: Wiley-Blackwell Publishing, Inc
Place of Publication: United States of America
ISSN: 2047-9980
Fields of Research (FoR) 2020: 310207 Statistical and quantitative genetics
Socio-Economic Objective (SEO) 2020: 200104 Prevention of human diseases and conditions
Peer Reviewed: Yes
HERDC Category Description: C1 Refereed Article in a Scholarly Journal
Appears in Collections:Journal Article
School of Environmental and Rural Science

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